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<h5 class="section-title" id="d11449197e183">Purpose</h5>
<p id="d11449197e185">To provide recommendations on appropriate clinical trial designs
in non–muscle-invasive
bladder cancer (NMIBC) based on current literature and expert consensus of the International
Bladder Cancer Group.
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<h5 class="section-title" id="d11449197e188">Methods</h5>
<p id="d11449197e190">We reviewed published trials, guidelines, meta-analyses, and
reviews and provided
recommendations on eligibility criteria, baseline evaluations, end points, study designs,
comparators, clinically meaningful magnitude of effect, and sample size.
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<h5 class="section-title" id="d11449197e193">Results</h5>
<p id="d11449197e195">NMIBC trials must be designed to provide the most clinically
relevant data for the
specific risk category of interest (low, intermediate, or high). Specific eligibility
criteria and baseline evaluations depend on the risk category being studied. For the
population of patients for whom bacillus Calmette-Guérin (BCG) has failed, the type
of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly
defined to make comparisons across trials feasible. Single-arm designs may be relevant
for the BCG-unresponsive population. Here, a clinically meaningful initial complete
response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors)
of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended.
For other risk levels, randomized superiority trial designs are recommended; noninferiority
trials are to be used sparingly given the large sample size required. Placebo control
is considered unethical for all intermediate- and high-risk strata; therefore, control
arms should comprise the current guideline-recommended standard of care for the respective
risk level. In general, trials should use time to recurrence or recurrence-free survival
as the primary end point and time to progression, toxicity, disease-specific survival,
and overall survival as potential secondary end points. Realistic efficacy thresholds
should be set to ensure that novel therapies receive due review by regulatory bodies.
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<h5 class="section-title" id="d11449197e198">Conclusion</h5>
<p id="d11449197e200">The International Bladder Cancer Group has developed formal
recommendations regarding
definitions, end points, and clinical trial designs for NMIBC to encourage uniformity
among studies in this disease.
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